title: Local alendronic acid elution increases net periimplant bone formation: a micro-CT analysis.
abstract: BACKGROUND
  Fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving implant fixation would improve the reliability and durability of certain reconstructive procedures.
  
  
  OBJECTIVE
  The purpose of this study was to determine the effect of local elution of the bisphosphonate alendronic acid on bone formation around porous titanium implants in an animal model.
  
  
  METHODS
  Porous-coated cylindrical rods were coated with either 0.2 mg or 1.0 mg alendronic acid before bilateral surgical implantation into the femoral intramedullary canals of 10 experimental dogs. Twelve weeks after surgery, the femora were harvested and scanned with micro-CT to quantify the percentage volume of bone within the immediate periimplant space. Four femora from two dogs were also processed for undecalcified thin-section histology and analysis with backscattered scanning electron microscopy. Three histologic sections from each of these four femora were anatomically matched with transverse micro-CT sections to enable direct comparison of the area fraction of bone within the periimplant space.
  
  
  RESULTS
  Compared with paired controls, micro-CT analysis showed that local elution of alendronic acid increased periimplant bone at both doses of 0.2 mg (+52%, p = 0.01) and 1.0 mg (+152%, p = 0.004) with 1.0 mg resulting in a 2.9-fold greater mean relative increase compared with 0.2 mg (p = 0.002). Micro-CT measurements of periimplant bone formation correlated very strongly with the backscattered scanning electron microscopy measurements (R = 0.965, p < 0.001).
  
  
  CONCLUSIONS
  Local elution of alendronic acid causes a dose-dependent net increase in periimplant bone formation in an animal model.
  
  
  CONCLUSIONS
  This concept has potential to improve the biologic fixation of porous reconstructive implants.
authors.affiliation: Jo Miller Orthopaedic Research Laboratory, Montreal General Hospital, 1650 Cedar Avenue, Room LS1-409, Montreal, QC, H3G1A4, Canada, john.bobyn@mcgill.ca.
authors.forename: J Dennis
authors.initials: JD
authors.lastname: Bobyn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Thompson
authors.forename: Letitia
authors.initials: L
authors.lastname: Lim
authors.forename: Jenny Ann
authors.initials: JA
authors.lastname: Pura
authors.forename: Kristian
authors.initials: K
authors.lastname: Bobyn
authors.forename: Michael
authors.initials: M
authors.lastname: Tanzer
mesh_terms: D019386:Alendronate / Q000008:administration & dosage*; D000497:Alloys; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D020099:Coated Materials, Biocompatible; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery; D008297:Male; D023421:Models, Animal; D016348:Osseointegration / Q000187:drug effects*; D016062:Porosity; D011474:Prosthesis Design; D019919:Prosthesis Implantation / Q000295:instrumentation*; D013997:Time Factors; D014025:Titanium; D055114:X-Ray Microtomography
chemical_list: D000497:Alloys; D050071:Bone Density Conservation Agents; D020099:Coated Materials, Biocompatible; C031462:titanium alloy (TiAl6V4); D014025:Titanium; D019386:Alendronate